This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. E2DISP, an engineered protein domain from Geobacillus stearothermophilus pyruvate dehydrogenase subunit E2, can be used to express N-terminal fusions of heterologous peptides or proteins. E2DISP self-assembles into 24 nm virus like particles (VLPs) displaying up to 60 copies of a foreign antigen. (1) Design HIV-E2 Envelope (Env) fusion proteins with conserved neutralization determinants and determine their effectiveness in eliciting neutralizing antibodies (NAbs). (2) Explore immunization strategies to elicit long lasting Th1 CD4, CTL memory responses while preserving sustained antibody responses. (3) Explore optimal presentation and co-administration of E2DISP VLPs with recombinant C3d-based adjuvants. (4) Optimize the use of pure and hybrid E2-HIV VLPs in prime-boost regimens with other vaccine delivery systems effective in boosting cellular immunity and NAb responses.